Rearrangement Reactions of α-Phenylcinnamic Acid Trimethylsilyl Esters Upon Electron Impact...
2
JOURNAL OF MASS SPECTROMETRY, VOL. 31, 823-824 (1996) JMS Letters Dear Sir, Rearrangement Reactions of a-Phenylcinnamic Acid TrimethylsilylEsters Upon Electron Impact Ionization: Practical and Theoretical Aspects* The Perkin condensation of benzaldehyde and phenylacetic acid in the presence of triethylamine gives an isomeric mixture of a-phenylcinnamic acids.' The isomeric ratio can be intlu- enced by the choice of solvent, reaction time and temperature of reflux.' Accurate composition can be determined by gas chromatography/mass spectrometry (GC/MS) after derivatiza- tion, i.e., through the determination of the trimethylsilyl or the tert-butyldimethylsilyl derivatives of the acidsS2 Upon electron impact (EI) ionization, several secondary transformations may proceed in the mass spectrometer, such as fragmentation and rearrangement reaction^.^ Identification of most fragments is usually straightforward and the sensitivity of routine GC/MS equipment is adequate, but rationalization of the rearrange- ment reactions may require more sophisticated high- resolution instrumentation. I 3 \ 1 In the mass spectra taken by GC/MS from the tri- methylsilyl esters of a-phenylcinnamic acid isomers, three peaks indicating rearrangement reactions were found [m/z 135, 152 and 237, each with appreciable intensities (8.5- 21.6%)].4 Although mechanisms leading to these fragments were offered in the cited paper, it turned out to be unrealistic for the lower fragments. Clearly, further investigation at high resolution was needed. Results of these measurements are given in this paper. In addition, a computational method is presented that has proved to be successful in predicting major fragmentation pathways. Synthesis of the pure or-phenylcinnamic acid isomers was based on the method of Fie~er.~ It involved heating a mixture of benzaldehyde (2 ml), phenylacetic acid (2.5 g), acetic anhy- dride (2 ml) and triethylamine (2 ml). On varying the duration of reflux, the isomeric composition varied. To obtain reason- able amounts of both isomers, reflux for 35 min was needed. For derivatization the silylating agent N,N- diethyltrimethylsilylamine (Fluka) was used. Samples of the pure isomers (10 mg) were dissolved in N,N-dimethyl- formamide (100 PI) and excess silylating agent (500 pl) was added at room temperature. The reaction was complete within 5 min. A 5 pl volume of this mixture was used for GC/MS analysis. The crystalline form of the silylated E isomer was used for high-resolution measurements. For the GC/MS analysis, a Hewlett-Packard Model 5890 gas chromatograph equipped with a quadrupole mass- * The work was presented at the 13th International Mass Spec- trometry Conference, Budapest, Hungary (poster: Mo C12). selective detector was applied. Data analysis was performed on an HP 5997 Chemstation attached to the apparatus. A 50 m HP1 capillary column was used; the solvent delay was 7 min, and a temperature program was applied from 523 to 623 K with a ramp of 4 K min-'. The electron energy was 70 eV. High-resolution mass spectrometric measurements were per- formed on crystalline samples on a Finnigan MAT 8430 mass spectrometer. The operating conditions were as follows: elec- tron energy, 70 eV; electron current, 50 pA; ion acceleration voltage, 3 kV; and temperature of ion source, 523 K. In high resolution (R = 1OOOO) mass measurements, per- fluorokerosene (PFK) was used as the reference standard. To explore bond strengths in the isomers, semi-empirical quantum chemical calculations were carried out with the AM1 method, included in the PcMol package.6 Full geomet- ric optimization was performed for the neutral molecules and the molecular ions of the isomers of the trimethylsilyl esters 1 (E, the ester and the j3-phenyl groups are on opposite sides; 2, the ester and the j3-phenyl groups are on the same side of the olefinic double bond). Bond orders were taken as a measure of bond strength. They were calculated for the optimized geome- tries and compared for the isomer pair. The mass-selective detector of the GC/MS instrument was used for initial mass spectrometric investigation. It turned out that the fragmentation pathways were the same for the two isomers, only the abundances of the fragment ions were differ- ent. The major fragments could be identified easily (Table 1). They were formed via the scission of the 0-Si, Si-C and C-0 bonds, or decarboxylation occurring with the sub- sequent loss of the olefinic hydrogen. These last two processes were the most important fragmentation pathways. Basic frag- mentation routes could be predicted by the semi-empirical (AM1) quantum chemical method. Bond order calculations on the geometrically optimized molecular ion revealed that the 0-Si bond was the weakest and the Si-CH, and the olefinic(C)-C(ester) bonds were easy to cleave (Table 2). A significant bond order decrease in the olefinic double bond (bc) on going from the AM1-optimized neutral mol- ecule to that of the radical cation showed that the molecular ion was formed via the removal of an electron from the olefin- ic n-bond. This ion was involved in theoretically predicted Table 1. The most abundant fragment ions, their rn/z values and relative peak intensities in the EI mass spectra of (E)- and (Z)a-phenylcinnamic acid trimethylsilylester isomers 1 Relative intensity (%) Fragment mi! E Z M +* 296 78.2 48.6 [M -'CHJ+ 281 64.1 43.2 2' 237 11.5 8.1 [M -'OSi(CH,),]+ 207 16.7 9.5 [M - 'C0,Si(CH3)3]+ 179 100.0 100.0 [M - Si(CH,),OH - CO]" 178 82.1 81.1 3b 152 15.4 12.2 4b 135 20.5 21.6 [(cH3)3siol' 89 5.1 8.1 [(CH,),SiOH]+ 75 19.2 24.3 C(CH,),Sil+ 73 70.5 100.0 [SiOH]+ 45 20.5 33.8 *See Scheme 1. See Scheme 2. CCC 1076-5174/96/070823-02 0 1996 by John Wiley & Sons, Ltd. Received 25 March 1996 Accepted 24 April 1996
Transcript of Rearrangement Reactions of α-Phenylcinnamic Acid Trimethylsilyl Esters Upon Electron Impact...
JOURNAL OF MASS SPECTROMETRY, VOL. 31, 823-824 (1996)
JMS Letters
Dear Sir,
Rearrangement Reactions of a-Phenylcinnamic Acid Trimethylsilyl Esters Upon Electron Impact Ionization: Practical and Theoretical Aspects*
The Perkin condensation of benzaldehyde and phenylacetic acid in the presence of triethylamine gives an isomeric mixture of a-phenylcinnamic acids.' The isomeric ratio can be intlu- enced by the choice of solvent, reaction time and temperature of reflux.' Accurate composition can be determined by gas chromatography/mass spectrometry (GC/MS) after derivatiza- tion, i.e., through the determination of the trimethylsilyl or the tert-butyldimethylsilyl derivatives of the acidsS2 Upon electron impact (EI) ionization, several secondary transformations may proceed in the mass spectrometer, such as fragmentation and rearrangement reaction^.^ Identification of most fragments is usually straightforward and the sensitivity of routine GC/MS equipment is adequate, but rationalization of the rearrange- ment reactions may require more sophisticated high- resolution instrumentation.
I
3 \
1
In the mass spectra taken by GC/MS from the tri- methylsilyl esters of a-phenylcinnamic acid isomers, three peaks indicating rearrangement reactions were found [m/z 135, 152 and 237, each with appreciable intensities (8.5- 21.6%)].4 Although mechanisms leading to these fragments were offered in the cited paper, it turned out to be unrealistic for the lower fragments. Clearly, further investigation at high resolution was needed. Results of these measurements are given in this paper. In addition, a computational method is presented that has proved to be successful in predicting major fragmentation pathways.
Synthesis of the pure or-phenylcinnamic acid isomers was based on the method of F i e ~ e r . ~ It involved heating a mixture of benzaldehyde (2 ml), phenylacetic acid (2.5 g), acetic anhy- dride (2 ml) and triethylamine (2 ml). On varying the duration of reflux, the isomeric composition varied. To obtain reason- able amounts of both isomers, reflux for 35 min was needed. For derivatization the silylating agent N,N- diethyltrimethylsilylamine (Fluka) was used. Samples of the pure isomers (10 mg) were dissolved in N,N-dimethyl- formamide (100 PI) and excess silylating agent (500 pl) was added at room temperature. The reaction was complete within 5 min. A 5 pl volume of this mixture was used for GC/MS analysis. The crystalline form of the silylated E isomer was used for high-resolution measurements.
For the GC/MS analysis, a Hewlett-Packard Model 5890 gas chromatograph equipped with a quadrupole mass-
* The work was presented at the 13th International Mass Spec- trometry Conference, Budapest, Hungary (poster: Mo C12).
selective detector was applied. Data analysis was performed on an HP 5997 Chemstation attached to the apparatus. A 50 m HP1 capillary column was used; the solvent delay was 7 min, and a temperature program was applied from 523 to 623 K with a ramp of 4 K min-'. The electron energy was 70 eV. High-resolution mass spectrometric measurements were per- formed on crystalline samples on a Finnigan MAT 8430 mass spectrometer. The operating conditions were as follows: elec- tron energy, 70 eV; electron current, 50 pA; ion acceleration voltage, 3 kV; and temperature of ion source, 523 K. In high resolution (R = 1OOOO) mass measurements, per- fluorokerosene (PFK) was used as the reference standard.
To explore bond strengths in the isomers, semi-empirical quantum chemical calculations were carried out with the AM1 method, included in the PcMol package.6 Full geomet- ric optimization was performed for the neutral molecules and the molecular ions of the isomers of the trimethylsilyl esters 1 (E, the ester and the j3-phenyl groups are on opposite sides; 2, the ester and the j3-phenyl groups are on the same side of the olefinic double bond). Bond orders were taken as a measure of bond strength. They were calculated for the optimized geome- tries and compared for the isomer pair.
The mass-selective detector of the GC/MS instrument was used for initial mass spectrometric investigation. It turned out that the fragmentation pathways were the same for the two isomers, only the abundances of the fragment ions were differ- ent. The major fragments could be identified easily (Table 1). They were formed via the scission of the 0-Si, Si-C and C-0 bonds, or decarboxylation occurring with the sub- sequent loss of the olefinic hydrogen. These last two processes were the most important fragmentation pathways. Basic frag- mentation routes could be predicted by the semi-empirical (AM1) quantum chemical method. Bond order calculations on the geometrically optimized molecular ion revealed that the 0-Si bond was the weakest and the Si-CH, and the olefinic(C)-C(ester) bonds were easy to cleave (Table 2).
A significant bond order decrease in the olefinic double bond (bc) on going from the AM1-optimized neutral mol- ecule to that of the radical cation showed that the molecular ion was formed via the removal of an electron from the olefin- ic n-bond. This ion was involved in theoretically predicted
Table 1. The most abundant fragment ions, their rn/z values and relative peak intensities in the EI mass spectra of (E)- and (Z)a-phenylcinnamic acid trimethylsilyl ester isomers 1
Relative intensity (%) Fragment m i ! E Z
M +* 296 78.2 48.6 [M -'CHJ+ 281 64.1 43.2 2' 237 11.5 8.1 [M -'OSi(CH,),]+ 207 16.7 9.5 [M - 'C0,Si(CH3)3]+ 179 100.0 100.0 [M - Si(CH,),OH - CO]" 178 82.1 81.1 3b 152 15.4 12.2 4 b 135 20.5 21.6 [(cH3)3siol' 89 5.1 8.1 [(CH,),SiOH]+ 75 19.2 24.3 C(CH,),Sil+ 73 70.5 100.0 [SiOH]+ 45 20.5 33.8
*See Scheme 1 . See Scheme 2.
CCC 1076-5174/96/070823-02 0 1996 by John Wiley & Sons, Ltd.
Received 25 March 1996 Accepted 24 April 1996
824 JMS LETTERS
Table 2. Bond orders in the molecular ions (roman type) and the natural molecules (italics) of the trimethylsilyl ester deriv- atives of stereoisomeric a- phenylcinnamic acids 1, determined for geometries optimized by AM1 semi- empirical quantum chemical method
1 Bond E Z
a-b 1.14 0.99 1.15 0.99 b c 1.45 1.82 1.44 1.84 b-e 0.94 0.94 0.94 0.92 c-d 0.93 0.94 0.93 0.94
e-f 1.04 7.72 1.04 1.71 f-g 0.67 0.65 0.67 0.65 g-i 0.88 0.87 0.88 0.87 g-j 0.88 0.88 0.88 0.88 g-k 0.91 0.88 0.91 0.88
c-h 1.20 1.02 1.20 1.02
1 2
Scheme 1. Route to fragment of m/z 237 (2).
and experimentally found fragmentation reactions and gave rise to various rearrangements reported in this paper.
As indicated in a recent paper,3 rearrangement reactions could take place upon EI of a-phenylcinnamic acid esters resulting in the formation of benzopyrilium ions. We also identified the relevant species (m/z 295), however, this rearrangement pathway was of minor importance. Here, the very labile 0-Si bond was not cleaved. In most other frag- mentation reactions of these compounds, the 0-Si bonds were cleaved preferentially (m/z 207). The high relative inten- sities of the peaks at m/z 281 and 179 indicated that Si-CH, and C(o1efinic)-C(ester) bond scissions were also facile.
High-resolution mass spectrometry revealed that fragments of m/z 135, 152 and 237 all contained Si. Isotopic satellites of m/z 137, 154 and 239 disappeared in the background of the mass spectra. However, they became clearly identifiable by high-resolution mass spectrometry. This observation can be interpreted by rearrangement reactions : after 0-Si and Si-CH, bond scissions, the Si-containing moieties migrated to other parts of the molecule. Migration was accompanied by CO, elimination in the case of the fragment of m/z 237 and a
1 3 4
Scheme 2. Route to fragments of m/z 152 (3) and 135 (4).
C(o1efinic)-Si bond was formed in place of the C(o1efinic)-C(ester) bond (Scheme 1).
A fragment of m/z 152 was formed similarly, except that the target of migration was a detached phenyl group and a dimethylphenylsilanol ion was produced. The loss of OH transformed m/z 152 into m/z 135 (Scheme 2).
Acknowledgements. The authors are grateful for the financial support provided by the National Science Foundation of Hungary through grant F4297/1992.
Yours,
(to whom correspondence should be addressed. Department of Organic Chemistry, Jbzsef Attila University, Dbm ter 8, H-6720 Szeged, Hungary GYULA HORVATH Institute for Drug Research, Berlini str. 47-49, H-1045 Budapest, Hungary
Department of Organic Chemistry, J6zsef Attila University, Dom ter 8, H-6720 Szeged, Hungary
ISTVAN PALINKC)
BELA TOROK
~~ ~ ~
References 1. H. Zimmermann and L. Ahramjian, J. Am. Chem. SOC. 81,2086
(1959). 2. I. PBlink6, Gy. Tasi, T. Kortvblyesi and B. Torok, froc. ECTOC-
7, CD-ROM Publications of the Royal Society, London (1996) (http ://www.ch.ic.ac.u k/ectoc/papers/).
3. K. P. Madhusudanan, V. S. Murthy, D. Fraisseand M. Becchi, Org. Mass Spectrom. 26, 505 (1 991).
4. B. Torok, 1. Palink6, Gy. Tasi, L. Nyerges and F. Bog&, J. Chro- matogr. A 668,353 (1 994).
5. L. Fieser, Experiments in Organic Chemistry. Heath, Boston
6. G. Tasi, I. Palink6, G. NBray-Szabd and J. HalBsz, P ~ M o l ~ ~ 3 . 1 , Semiempirical Calculations on Microcomputers. Distributed by Chemicro, Budapest (1 992).
(1955).
